Suppression of human T cell activation by derivatives of glycerol monolaurate.
Suppression of human T cell activation by derivatives of glycerol monolaurate.
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DOI：
10.1038/s41598-021-88584-y
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发表时间：
2021-04-26
影响因子：
4.6
通讯作者：
Houtman JCD
中科院分区：
文献类型：
--
作者：
Fosdick MG;Chheda PR;Tran PM;Wolff A;Peralta R;Zhang MY;Kerns R;Houtman JCD
单月桂酸甘油（GML）是一种天然存在的单甘油酯，因其抗菌特性而在商业上广泛使用。有趣的是，一些研究表明，GML不仅具有抗菌特性，而且还是一种抗炎剂。GML抑制外周血单个核细胞增殖，抑制T细胞受体（TCR）诱导的信号事件。在这项研究中，我们进行了广泛的结构活性关系分析，以研究GML抑制人类T细胞活化所必需的结构成分。用GML类似物处理人T细胞，其酰基链长度、头基团、酰基链的连接和月桂酸基团的数量不同。然后检测处理过的细胞在膜动力学、LAT聚类、钙信号和细胞因子产生方面的变化。我们发现含有12-14个碳的酰基链、极性头基、酯链和任何位置的月桂酸酯基都是GML抑制蛋白质聚集、钙信号传导和细胞因子产生所必需的。去除甘油头基团或用氮取代酯链可以阻止衍生物介导的蛋白质簇形成和钙信号的抑制，同时仍然抑制tcr诱导的细胞因子的产生。这些发现扩大了我们目前对GML的作用机制和GML作为一种新型免疫抑制剂所需的作用机制的理解。
Glycerol monolaurate (GML), a naturally occurring monoglyceride, is widely used commercially for its antimicrobial properties. Interestingly, several studies have shown that GML not only has antimicrobial properties but is also an anti-inflammatory agent. GML inhibits peripheral blood mononuclear cell proliferation and inhibits T cell receptor (TCR)-induced signaling events. In this study, we perform an extensive structure activity relationship analysis to investigate the structural components of GML necessary for its suppression of human T cell activation. Human T cells were treated with analogs of GML, differing in acyl chain length, head group, linkage of acyl chain, and number of laurate groups. Treated cells were then tested for changes in membrane dynamics, LAT clustering, calcium signaling, and cytokine production. We found that an acyl chain with 12–14 carbons, a polar head group, an ester linkage, and a single laurate group at any position are all necessary for GML to inhibit protein clustering, calcium signaling, and cytokine production. Removing the glycerol head group or replacing the ester linkage with a nitrogen prevented derivative-mediated inhibition of protein cluster formation and calcium signaling, while still inhibiting TCR-induced cytokine production. These findings expand our current understanding of the mechanisms of action of GML and the of GML needed to function as a novel immunosuppressant.
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影响因子：
3.7
作者：
Schlievert, Patrick M.;Peterson, Marnie L.
通讯作者：
Peterson, Marnie L.
DOI：
10.5402/2011/949686
发表时间：
2011
期刊：
ISRN pharmacology
影响因子：
--
作者：
Liau KM;Lee YY;Chen CK;Rasool AH
通讯作者：
Rasool AH
影响因子：
4.9
作者：
SCHLIEVERT, PM;DERINGER, JR;NOVICK, RP
通讯作者：
NOVICK, RP
影响因子：
3.7
作者：
Zhang, Michael S.;Houtman, Jon C. D.
通讯作者：
Houtman, Jon C. D.
影响因子：
7.3
作者：
Zhang, Michael S.;Tran, Phuong M.;Houtman, Jon C. D.
通讯作者：
Houtman, Jon C. D.